Dina S El-Agamy1. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Abstract
OBJECTIVES: This study aimed to evaluate the potential protective effects of pirfenidone (PFD) against concanavalin A (Con A)-induced hepatitis in mice. METHODS: Autoimmune model of hepatitis was established using single intravenous injection of Con A. Mice were randomly assigned into four groups as follows: control group; Con A group; and two groups, receiving PFD in two dose levels (200, 300 mg/kg) for 5 days before Con A administration. Extent of hepatitis was studied using biochemical, histopathological and immunohistochemical estimations. KEY FINDINGS: Hepatitis was clearly evident through extensive hepatocellular lesions and elevated levels of serum transaminases, alkaline phosphatase and lactate dehydrogenase. Con A induced an imbalance between oxidant and antioxidant status in the hepatic tissue. Furthermore, Con A significantly elevated hepatic nuclear factor kappa B (NF-κB) expression and inflammatory cytokines levels (tumour necrosis factor-alpha, interleukin-6 and nitric oxide). PFD pretreatment potently ameliorated all these pathological changes. CONCLUSIONS: Pirfenidone hepatoprotective activity may be mediated through its antioxidant ability that suppresses NF-κB activation signalling pathways suggesting that PFD may be a new candidate for treatment of acute hepatitis.
OBJECTIVES: This study aimed to evaluate the potential protective effects of pirfenidone (PFD) against concanavalin A (Con A)-induced hepatitis in mice. METHODS: Autoimmune model of hepatitis was established using single intravenous injection of Con A. Mice were randomly assigned into four groups as follows: control group; Con A group; and two groups, receiving PFD in two dose levels (200, 300 mg/kg) for 5 days before Con A administration. Extent of hepatitis was studied using biochemical, histopathological and immunohistochemical estimations. KEY FINDINGS:Hepatitis was clearly evident through extensive hepatocellular lesions and elevated levels of serum transaminases, alkaline phosphatase and lactate dehydrogenase. Con A induced an imbalance between oxidant and antioxidant status in the hepatic tissue. Furthermore, Con A significantly elevated hepatic nuclear factor kappa B (NF-κB) expression and inflammatory cytokines levels (tumour necrosis factor-alpha, interleukin-6 and nitric oxide). PFD pretreatment potently ameliorated all these pathological changes. CONCLUSIONS:Pirfenidone hepatoprotective activity may be mediated through its antioxidant ability that suppresses NF-κB activation signalling pathways suggesting that PFD may be a new candidate for treatment of acute hepatitis.
Authors: Dina S El-Agamy; Ahmed A Shaaban; Hamdi H Almaramhy; Sarah Elkablawy; Mohamed A Elkablawy Journal: Front Pharmacol Date: 2018-03-28 Impact factor: 5.810